Regulators of Contact Stimulation of Migration in Testis Nascent Myotubes

• Applicant: Dr. Maik Christian Bischoff
• Subject Area: Developmental Biology ; Cell Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 466788046

Collective cell migration plays a crucial role in development, wound healing and metastasis. During my doctorate I established a new model for collective cellular motility, the Drosophila testis nascent myotube system. Using state-of-the-art live-cell imaging as well as pharmacological and genetic perturbation, I identified a new mechanism of contact-stimulated collective migration (CSM) in which a contact-dependent asymmetry of cell-matrix adhesion acts as a major switch to drive directional motion towards the free space, whereas contractile actin cables contribute to the integrity of the migrating muscle cell cluster. In the proposed project I will address how this intricate behaviour is regulated at the molecular level. Previously, it could be shown to be dependent of differential cell-cell contact dependent regulation of matrix-adhesion stability, apparently orchestrated by the Rho-family GTPases Rac2 and Cdc42. RBD-based biosensors will be created and applied to assess where Rac2 and Cdc42 are active on a subcellular level. Single-cell sequencing analysis of pre-migratory and migratory muscle cells will be applied, to assess which genes are upregulated and may be upstream of local GTPase activation. Subsequently, bioinformatically prioritized candidates will be targeted by RNAi and cell-specific CRISPR/CAS9 techniques. Preliminary results show the collective migration of testis nascent myotubes to depend on MMP2. Therefore, myotubes seem to use mechanics during development, known from invasive cancer cell motility. To fully assess the influence of the microenvironment that presumably has to be degraded, the composition and source-tissues of the ECM (extracellular matrix) will be addressed. The contribution of ECM-composition on migration and invasive dynamics will be investigated by using tissue specific RNAi in adjacent tissues.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Mark Peifer, Ph.D.